ECEESPE2025 Poster Presentations Endocrine Related Cancer (76 abstracts)
Unraveling the role of autophagy in adrenocortical carcinoma
Sofia B. Oliveira 1 2 3 , Marta Alves 1 , Diana Sousa 1 , 4 , Madalena Santos 1 , Elisabete Rios 5 , Tiago Nunes da Silva 6 , Valeriano Leite 6 , Laura-Sophie Landwehr 7 , Sofia Pereira 1 & Duarte Pignatelli 2 3 8
1Unit for Multidisciplinary Research in Biomedicine - School of Medicine and Biomedical Sciences (UMIB-ICBAS); Laboratory for Integrative and Translational Research in Population Health (ITR), Porto, Portugal; 2Institute for Reseach and Innovation in Health (i3S), University of Porto, Porto, Portugal; 3Unidade Local de Saúde de São João (ULS de São João), Departamento de Endocrinologia, Porto, Portugal; 4Faculdade de Medicina Dentária de Viseu – Universidade Católica Portuguesa (UCP), Viseu, Portugal; 5Department of Pathology, Faculty of Medicine of the University of Porto, Porto, Portugal; 6Serviço de Endocrinologia, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal, Lisboa, Portugal; 7Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University Würzburg, Würzburg, Germany; 8Department of Biomedicine, Faculty of Medicine, University of Porto, Porto, Portugal
JOINT2839
Adrenocortical carcinoma (ACC) represents the second most lethal endocrine malignancy. This poor prognosis is mainly related to the difficulty in establishing an early diagnosis and the limited efficacy of mitotane which is the only approved pharmacological treatment. Autophagy, a dynamic cellular process that degrades and/or recycle various cellular components, plays a dual role in tumorigenesis by contributing for both cell survival and death. However, its role in adrenocortical tumors (ACT) remains largely unexplored. Therefore, we aimed to assess the expression of LC3, a central autophagy regulatory protein, in ACT, to verify its potential for ACC diagnosis. Additionally, we investigated the role of autophagy in ACC treatment. For that, the expression of LC3 was evaluated by immunohistochemistry (IHC) in paraffin-embedded tissues of ACC (n = 10) and adrenocortical adenoma (ACA) (n = 15). The LC3 dot-like staining pattern was evaluated by counting LC3-positive cells in tumor hot-spots, with at least 1000 cells analyzed per ACT case. In addition, to explore the role of autophagy in ACC treatment, the ACC cell-line (JIL-2266) was treated with mitotane either alone or in combination with bafilomycin, a late-stage autophagic flux inhibitor. Cellular density and expression of LC3I/II and p62 were assessed by Trypan-Blue assay and Western-Blot, respectively. LC3 dot-like staining was observed in all ACC and in 87% of ACA (13/15). The percentage of LC3 positive cells was significantly higher in ACC compared to ACA (ACC vs ACA: 13% vs 2%, P<0. 001). Indeed, LC3 protein appears to be an excellent marker to differentiate ACC from ACA, with an area under ROC of 0. 900. In vitro, studies showed that mitotane treatment reduced ACC cell density and increased LC3-II levels compared to the vehicle. Moreover, LC3-II expression was even higher when cells were co-treated with mitotane and bafilomycin, compared to mitotane treatment alone. Our results suggest that autophagy play an important role in ACT. Indeed, LC3 dot-like expression, which has been correlated with autophagy induction, was present in most ACT. Notably, LC3 positive cells appear to be associated with malignancy in ACT. Additionally, our findings indicate that mitotane treatment modulates autophagy by the induction of autophagosome synthesis. Future research will validate these results in a larger ACT patients’ cohort, along with more detailed mechanistic studies.
FundingFCT (UIDB/00215/2020, UIDP/00215/2020, LA/P/0064/2020, 2022. 13324. BD).
Volume 110
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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